crossing96/oncoscreening huggingface dataset:
Identification of a novel immune microenvironment signature predicting survival and therapeutic options for bladder cancer.	Few studies have investigated the potential of tumor immune microenvironment genes as indicators of urinary bladder cancer. Here, we sought to establish an immune-related gene signature for determining prognosis and treatment options. We developed a ten-gene tumor immune microenvironment signature and evaluated its prognostic capacity on internal and external cohorts. Multivariate Cox regression and nomogram analyses revealed the prognostic risk model as an independent and effective indicator of prognosis. We observed lower proportions of CD8+ T cells, dendritic cells, regulatory T cells, higher proportions of macrophages and neutrophils in high UBC risk group. UBC tissues with high-risk score tend to exhibit high TP53 and RB1 mutation rates, high PD1/PD-L1 expression and poor-survival basal squamous subtypes, while those with low-risk score tend to have high FGFR3 mutation rates and luminal papillary subtypes. Unexpectedly, we found a highly significant positive correlation between glycolytic genes and risk score, highlighting metabolic competition in tumor ecosystem and potential therapeutic avenues. Our study thus revealed a tumor immune microenvironment signature for predicting prognostic and response to immune checkpoint inhibitors against bladder cancer. Prospective studies are required to further test the predictive capacity of this model.	bladder
Role of microRNA-381 in bladder cancer growth and metastasis with the involvement of BMI1 and the Rho/ROCK axis.	BACKGROUND: Emerging evidence has noted the important participation of microRNAs (miRNAs) in several human diseases including cancer. This research was launched to probe the function of miR-381 in bladder cancer (BCa) progression. METHODS: Twenty-eight patients with primary BCa were included in this study. Cancer tissues and the adjacent normal tissues were obtained. Aberrantly expressed miRNAs in BCa tissues were analyzed using miRNA microarrays. miR-381 expression in the bladder and paired tumor tissues, and in BCa and normal cell lines was determined. The target relationship between miR-381 and BMI1 was predicted online and validated through a luciferase assay. Gain-of-functions of miR-381 and BMI1 were performed to identify their functions on BCa cell behaviors as well as tumor growth in vivo. The involvement of the Rho/ROCK signaling was identified. RESULTS: miR-381 was poor regulated in BCa tissues and cells (all p < 0.05). A higher miR-381 level indicated a better prognosis of patients with BCa. Artificial up-regulation of miR-381 inhibited proliferation, invasion, migration, resistance to apoptosis, and tumor formation ability of BCa T24 and RT4 cells (all p < 0.05). miR-381 was found to directly bind to BMI1 and was negatively correlated with BMI1 expression. Overexpression of BMI1 partially blocked the tumor suppressing roles of miR-381 in cell malignancy and tumor growth (all p < 0.05). In addition, miR-381 led to decreased RhoA phosphorylation and ROCK2 activation, which were also reversed by BMI1 (all p < 0.05). Artificial inhibition of the Rho/ROCK signaling blocked the functions of BMI1 in cell growth and metastasis (all p < 0.05). CONCLUSION: The study evidenced that miR-381 may act as a beneficiary biomarker in BCa patients. Up-regulation of miR-381 suppresses BCa development both in vivo and in vitro through BMI1 down-regulation and the Rho/ROCK inactivation.	bladder
Hospital volume is associated with postoperative mortality after radical cystectomy for treatment of bladder cancer.	OBJECTIVE: To contribute to the debate regarding the minimum volume of radical cystectomies (RCs) that a hospital should perform by evaluating the association between hospital volume (HV) and postoperative mortality. PATIENTS AND METHODS: Patients who underwent RC for bladder cancer between 1 January 2008 and 31 December 2018 were retrospectively identified from the Netherlands Cancer Registry. To create a calendar-year independent measure, the HV of RCs was calculated per patient by counting the RCs performed in the same hospital in the 12 months preceding surgery. The relationship of HV with 30- and 90-day mortality was assessed by logistic regression with a non-linear spline function for HV as a continuous variable, which was adjusted for age, tumour, node and metastasis (TNM) stage, and neoadjuvant treatment. RESULTS: The median (interquartile range; range) HV among the 9287 RC-treated patients was 19 (12-27; 1-75). Of all the included patients, 208 (2.2%) and 518 (5.6%) died within 30 and 90 days after RC, respectively. After adjustment for age, TNM stage and neoadjuvant therapy, postoperative mortality slightly increased between an HV of 0 and an HV of 25 RCs and steadily decreased from an HV of 30 onwards. The lowest risks of postoperative mortality were observed for the highest volumes. CONCLUSION: This paper, based on high-quality data from a large nationwide population-based cohort, suggests that increasing the RC volume criteria beyond 30 RCs annually could further decrease postoperative mortality. Based on these results, the volume criterion of 20 RCs annually, as recently recommended by the European Association of Urology Guideline Panel, might therefore be reconsidered.	bladder
Curative Radiotherapy in Elderly Patients With Muscle Invasive Bladder Cancer: The Prognostic Role of Sarcopenia.	BACKGROUND/AIM: To evaluate the impact of sarcopenia in muscle invasive bladder cancer (MIBC) elderly patients submitted to curative radiotherapy. PATIENTS AND METHODS: Patients received radiotherapy between 2013 and 2018, and the skeletal muscle index was calculated to classify them as sarcopenic or non-sarcopenic. Primary endpoints were overall survival (OS), cancer specific survival (CSS), 90-day mortality and toxicity. RESULTS: A total of 28 patients with a median age of 85 years met our inclusion criteria and 8 of them were sarcopenic. With a median prescribed dose of 61 Gy and a median follow-up of 24.5 months, OS rates in the sarcopenic and non-sarcopenic groups were 100% and 84.4% at 3 months, 57.1% and 56.6% at 12 months, 38.1% and 50.3% at 24 months and 38.1% and 33.5% at 48 months, respectively; the CSS rates were 100% and 94.1% at 3 months and 68.6% and 88.2% at 12, 24 and 48 months, respectively. The actuarial 90-day mortality rate was 17.9% for the whole cohort, and 20% and 12.5% for the non-sarcopenic and sarcopenic groups, respectively. The radio-induced toxicity was similar in both groups. CONCLUSION: Sarcopenia cannot be considered a negative prognostic factor for MIBC elderly patients treated with external beam radiotherapy. Irradiation is therefore a feasible and effective choice for these patients, especially if unfit for surgery.	bladder
Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes.	Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA, RB1, FGFR3, KMT2C, MACF1, RYR2, and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.	bladder
[SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION AS A SIDE EFFECT OF CHEMOTHERAPY FOR URACHAL CARCINOMA: A CASE REPORT].	A 54-year-old woman was admitted to our hospital complaining of gross hematuria and difficulty urinating. Cystoscopy revealed a tumor 4 cm in size with calcification on top of the bladder. After diagnosis of urachal carcinoma by transurethral resection of the bladder, partial cystectomy with en bloc resection of the median umbilical ligament and pelvic lymphadenectomy was performed. Pathological diagnosis confirmed urachal carcinoma, pT3b, ly1, v0, pN1, RM0. TS-1 and cisplatin chemotherapy (TS-1 at 100 mg/day on days 1-21, CDDP at 60 mg/m(2) on day 8) was administered. On day 13, the patient was admitted because of consciousness disorder (Glasgow Coma Scale E2V1M4). Hyponatremia (Na 109 mEq/l) and renal excretion of sodium were present and the patient was diagnosed with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by chemotherapy. Serum sodium level and her consciousness level gradually improved after administration of 3% saline. SIADH caused by chemotherapy containing cisplatin is a relatively rare, but potentially serious adverse effect that requires close attention.	bladder
Social and Clinical Correlates of Neoadjuvant Chemotherapy in Medicare Beneficiaries With Muscle Invasive Bladder Cancer From 2004-2015.	OBJECTIVE: To assess social and clinical correlates of neoadjuvant chemotherapy (NAC) utilization among Medicare beneficiaries. MATERIALS AND METHODS: A cohort of SEER-Medicare (2004-2015) patients with muscle-invasive bladder cancer treated by radical cystectomy were stratified into 3-groups: standard of care NAC (cisplatin-based combination), non-standard of care NAC, and upfront cystectomy. Multivariable logistic regression analysis was used to assess social, demographic and clinical correlates of each treatment category. Survival analyses were performed to compare propensity matched treatment groups. RESULTS: In total, 6214 patients were identified with a median follow-up of 21 [IQR 7-54] months. NAC utilization increased from 10.7% to 39.1%, between 2004 and 2015, largely due to increased use of standard of care regimens. The most commonly used nonstandard regimen was gemcitabine/carboplatin (50.2%). Older age, Hispanic and Black race, lower socioeconomic status, and contraindications to cisplatin were associated with increased odds of receiving nonstandard of care NAC compared to standard of care. Standard of care NAC was associated with improved overall survival HR 0.85 (95% CI 0.76, 0.94) and HR 0.75 (95% CI 0.63, 0.89) compared to both upfront cystectomy and nonstandard of care NAC, respectively. CONCLUSION: NAC utilization has increased to nearly 40%; however, the use of non-standard of care NAC regimen have persisted (~8%). Cisplatin-ineligibility, older age, race/ethnicity, and lower socioeconomic status were correlated with nonstandard of care NAC, which provided no clinical benefit at the risk of potential harm. In accordance with current clinical guidelines, cisplatin-ineligible patients should be considered for timely upfront cystectomy or novel clinical trials.	bladder
Follow-up in non-muscle invasive bladder cancer: facts and future.	Patients with non-muscle invasive bladder cancer (NMIBC) have high recurrence and progression rates in spite of tumor resection and adjuvant instillation therapy. To detect recurrences and progression, these patients remain under frequent follow-up. Follow-up, however, is not well defined. Frequency and duration of follow recommendations are based on low levels of evidence, which is illustrated by clear differences in these recommendations per guideline, even when specified per risk group. Additionally, follow-up is recommended with cystoscopy and cytology in selected patients, which both have clear limitations. Fact is that follow-up in NMIBC is too frequent, with low levels of evidence and suboptimal tools, and it is patient unfriendly and costly. Improved cystoscopy techniques are unproven or impractical in the outpatient follow-up setting. Urinary markers have been around for decades, but never widely used in clinical practice. New (epi)genetic markers, however, could play a significant role in future follow-up of NMIBC. They have been shown to have very high negative predictive values for recurrences in follow-up of NMIBC, especially high-grade recurrences. Several studies suggested that these markers could be used to adapt follow-up cystoscopy frequency. What still needs study and confirmation is the cost-effectiveness of the use of these markers, which is highly dependent on health care costs per country and marker price. In all, however, implementation of these new urinary markers after confirmation of current results might significantly reduce patient burden and health care costs in the near future without reducing quality.	bladder
[Adjuvant radiotherapy after radical cystectomy for muscle-invasive bladder cancer].	"OBJECTIVES: Locoregional relapse (LRR) after cystectomy is a common early event associated with poor prognosis. The role of radiotherapy as an adjunct to radical cystectomy is not well-defined. The aim of this critical literature review is to provide an overview of the elements in favor of adjuvant radiation for patients treated for muscle-invasive bladder cancer. MATERIAL AND METHODS: An exhaustive review of the literature was carried out using the Pubmed search tool with the following keywords: ""radiotherapy"" [Mesh], ""adjuvant"" [Mesh], ""local recurrence"" [Mesh], ""Bladder cancer"" [Mesh]. RESULTS: Several recent publications have led to the development of a nomogram that predicts the risk of LRR, in order to identify patients for which adjuvant radiotherapy could be beneficial. Several randomized trials seem to suggest a benefit of radiotherapy, in particular when combined with chemotherapy, in terms of reducing LRR, and may even improve overall survival, with good safety profile. However, there are many biases and the interest of adjuvant radiotherapy in urothelial carcinomas remains debated. CONCLUSION: Prospective trials evaluating adjuvant radiotherapy with current techniques should be undertaken."	bladder
Trends of incidence and prognosis of upper tract urothelial carcinoma.	The purpose of this study was to investigate trends in the incidence of upper tract urothelial carcinoma (UTUC) in patients and to establish a reliable and practical nomogram based on significant clinical factors to predict the overall survival (OS) and cancer-specific survival (CSS) of UTUC patients. The Surveillance, Epidemiology, and End Results (SEER) database was used to extract data on UTUC patients between 1988 and 2015. Incidence was calculated using Joinpoint regression software, and trends were quantified by annual percentage change (APC). A nomogram was constructed using R software to predict the OS and CSS probabilities for individual patients. From 1988 to 2015, the incidence of UTUC showed a downward trend (1988: 1.57/100,000 to 2015: 1.51/100,000; APC=-0.1). After stratification according to sex, age and primary site, we found that the incidences of UTUC in males, patients 70+ years old and the renal pelvis were higher than those in females, patients <70 years old and ureter cancer patients. In the training cohort, the nomogram established based on multivariate Cox regression results showed better OS and CSS accuracy (OS: C-index=0.701, AUC=0.736; CSS: C-index=0.729, and AUC=0.688) than SEER stage. In addition, the calibration curves showed good consistency between the predicted and actual 3-, 5- and 10-year OS and CSS rates of the nomogram. In the past 30 years, the incidence of UTUC has shown a general downward trend, and the prognostic nomogram we established can provide a personalized risk assessment for the survival of UTUC patients.	bladder
Evaluation of the New American Urological Association Guidelines Risk Classification for Hematuria.	PURPOSE: Microhematuria is a prevalent condition and the American Urological Association has developed a new risk-stratified approach for the evaluation of patients with microhematuria. Our objective was to provide the first evaluation of this important guideline. MATERIALS AND METHODS: This multinational cohort study combines contemporary patients from 5 clinical trials and 2 prospective registries who underwent urological evaluation for hematuria. Patients were stratified into American Urological Association risk strata (low, intermediate or high risk) based on sex, age, degree of hematuria, and smoking history. The primary end point was the incidence of bladder cancer within each risk stratum. RESULTS: A total of 15,779 patients were included in the analysis. Overall, 727 patients (4.6%) were classified as low risk, 1,863 patients (11.8%) were classified as intermediate risk, and 13,189 patients (83.6%) were classified as high risk. The predominance of high risk patients was consistent across all cohorts. A total of 857 bladder cancers were diagnosed with a bladder cancer incidence of 5.4%. Bladder cancer was more prevalent in men, smokers, older patients and patients with gross hematuria. The cancer incidence for low, intermediate and high risk groups was 0.4% (3 patients), 1.0% (18 patients) and 6.3% (836 patients), respectively. CONCLUSIONS: The new risk stratification system separates hematuria patients into clinically meaningful categories with differing likelihoods of bladder cancer that would justify evaluating the low, intermediate and high risk groups with incremental intensity. Furthermore, it provides the relative incidence of bladder cancer in each risk group which should facilitate patient counseling regarding the risks and benefits of evaluation for bladder cancer.	bladder
Implications of androgen receptor and FUS expression on tumor progression in urothelial carcinoma.	Androgen receptor (AR) interact with many pathways involved in bladder cancer development and progression. FUS (fused in liposarcoma), a multifunctional protein essential for different cellular processes, has been demonstrated as a key link between androgen receptor signaling and cell-cycle progression in prostate cancer but has not been examined in urothelial carcinoma (UC) despite an intimate association between prostate and bladder carcinogenesis. AIM: To examine the immunohistochemical expression of AR and FUS in urothelial carcinoma in relation to prognostic parameters and to extrapolate any possible link between the expression of both markers and tumor progression. STUDY DESIGN: Retrospective study using immunohistochemical staining for AR and FUS on (88) cases of urothelial carcinoma. RESULTS: AR shows statistically significant relations with late tumor stage, high tumor grade, and non-papillary tumor pattern. On the other hand, FUS expression correlates with early tumor stage, low tumor grade and papillary pattern. An inverse relation is found between AR and FUS expression (p=0.001). Cases with high AR IHC expression show statistically significant shorter OS, RFS and PFS compared to cases with low AR expression. Cases with high FUS IHC expression reveal statistically significant longer OS, RFS and PFS compared to cases with low FUS expression. CONCLUSION: FUS expression is associated with favorable prognostic parameters of UC. A possible interaction is suggested between FUS and AR pathways involved in urothelial cancer progression. Manipulating FUS levels and androgen deprivation therapy can provide new promising targets for treatment trials.	bladder
Wnt signalling pathway in bladder cancer.	Bladder cancer (BC) is one of the most common tumours of the urinary system and is also known as a highly malignant tumour. In addition to conventional diagnosis and treatment methods, recent research has focused on studying the molecular mechanisms related to BC, in the hope that new, less toxic and effective targeted anticancer drugs and new diagnostic markers can be discovered. It is known that the Wingless (Wnt) signalling pathway and its related genes, proteins and other substances are involved in multiple biological processes of various tumours. Clarifying the contribution of the Wnt signalling pathway in bladder tumours will help establish early diagnosis indicators, develop new therapeutic drugs and evaluate the prognosis for BC. This review aims to summarise previous studies related to BC and the Wnt signalling pathway, with a focus on exploring the participating substances and their mechanisms in the regulation of the Wnt signalling pathway to better determine how to promote new chemotherapeutic drugs, potential therapeutic targets and diagnostic biomarkers.	bladder
Urinary biomarkers to mitigate diagnostic delay in bladder cancer during the COVID-19 era.	The COVID-19 pandemic has resulted in a substantial increase in waiting times for cystoscopies, prompting concerns of delayed diagnoses and substandard surveillance of bladder cancer. Expanding the role of urinary biomarkers in diagnostic and surveillance pathways could be a strategy to address this problem, and several novel biomarkers have shown promise for this purpose.	bladder
Radical Cystectomy Against Intravesical BCG for High-Risk High-Grade Nonmuscle Invasive Bladder Cancer: Results From the Randomized Controlled BRAVO-Feasibility Study.	PURPOSE: High-grade nonmuscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease. Treatments include intravesical maintenance Bacillus Calmette-Guerin (mBCG) and radical cystectomy (RC). We wanted to understand whether a randomized trial comparing these options was possible. MATERIALS AND METHODS: We conducted a two-arm, prospective multicenter randomized study to determine the feasibility in Bacillus Calmette-Guerin-naive patients. Participants had new high-risk HRNMIBC suitable for both treatments. Random assignment was stratified by age, sex, center, stage, presence of carcinoma in situ, and prior low-risk bladder cancer. Qualitative work investigated how to maintain equipoise. The primary outcome was the number of patients screened, eligible, recruited, and randomly assigned. RESULTS: We screened 407 patients, approached 185, and obtained consent from 51 (27.6%) patients. Of these, one did not proceed and therefore 50 were randomly assigned (1:1). In the mBCG arm, 23/25 (92.0%) patients received mBCG, four had nonmuscle invasive bladder cancer (NMIBC) after induction, three had NMIBC at 4 months, and four received RC. At closure, two patients had metastatic BC. In the RC arm, 20 (80.0%) participants received cystectomy, including five (25.0%) with no tumor, 13 (65.0%) with HRNMIBC, and two (10.0%) with muscle invasion in their specimen. At follow-up, all patients in the RC arm were free of disease. Adverse events were mostly mild and equally distributed (15/23 [65.2%] patients with mBCG and 13/20 [65.0%] patients with RC). The quality of life (QOL) of both arms was broadly similar at 12 months. CONCLUSION: A randomized controlled trial comparing mBCG and RC will be challenging to recruit into. Around 10% of patients with high-risk HRNMIBC have a lethal disease and may be better treated by primary radical treatment. Conversely, many are suitable for bladder preservation and may maintain their prediagnosis QOL.	bladder